不同剂量黄芪组方的拯阳汤对小鼠免疫功能的影响

目的 探讨不同剂量黄芪(47.62％、15.87％、5.29％)组方拯阳汤对小鼠免疫功能的影响。方法 建立受氢化可的松(HC)免疫抑制动物模型,采用MTT法检测腹腔巨噬细胞(Mφ)的活性、ConA诱导的脾脏T淋巴细胞转化增殖;以YAC-1为靶细胞用LDH释放改良法测定小鼠脾脏NK细胞和LAK细胞毒活性。结果 不同剂量黄芪组方的拯阳汤具有不同程度地拮抗HC对小鼠腹腔Mφ的活性的抑制,拮抗HC对小鼠脾脏T淋巴细胞转化的抑制,拮抗HC对小鼠脾脏NK细胞和LAK细胞毒活性的抑制。结论 拯阳汤具有拮抗HC对小鼠细胞免疫抑制的作用。     

Complex regional pain syndrome and dysautonomia in a 14‐year‐old girl responsive to therapeutic plasma exchange

Reflex sympathetic dystrophy, also known as complex regional pain syndrome (CRPS), has recently been shown to be associated with autoantibodies against β2‐adrenergic and muscarinic M2 receptors. In addition to pain and sudomotor/vasomotor symptoms, dysautonomia is also observed in a subset of CRPS patients. Despite its severity, there are few effective therapies for CRPS described to date. We report a case of a 14‐year‐old girl with CRPS of her right leg and dysautonomia (gastroparesis, postural tachycardia) refractory to multiple therapies, successfully treated with therapeutic plasma exchange (TPE) with albumin replacement. The patient, who has serum anti β2‐adrenergic and muscarinic M2 receptor autoantibodies in addition to nicotinic acetylcholine receptor ganglionic autoantibodies, underwent an initial course of five TPEs over a 2‐week period. She demonstrated a clinical response to TPE as manifested by a rapid improvement in her fatigue and gastroparesis, with a gradual yet significant improvement in her leg pain and sudomotor/vasomotor flares. Following the loading procedures, the patient was treated with rituximab. She continues to require periodic TPE to maintain a remission, with additional immunosuppression being considered long term. Although further studies are needed, TPE (in combination with immunosuppression) may be an appropriate therapy for CRPS patients with detectable autoantibodies, as it is for better characterized diseases with autoantibodies against neuronal surface receptors such as myasthenia gravis or Lambert Eaton myasthenic syndrome. J. Clin. Apheresis 31:368–374, 2016. © 2015 Wiley Periodicals, Inc.     

Facial transplantation: adding to the reconstructive options after severe facial injury and disease

The ability to reconstruct complex facial injuries is still a considerable challenge despite the development of microsurgical techniques. The reconstructive options for conditions such as panfacial burns are severely limited. The result after multiple surgical procedures in this group is often poor in terms of function and cosmesis. Facial transplantation provides a potential solution, but opinion is currently divided about the extent to which the potential benefits to the quality of life can be justified when weighed against the technical, psychological and immunological risks. This paper reviews the current status of the debate and argues that a rigorous research strategy is the only logical basis for countering the ethical objections to a procedure that offers considerable benefits over existing reconstructive options.     

Skin infections in Egyptian renal transplant recipients

N.I. Bakr, E. El‐Sawy, A.F. Hamdy, M.A. Bakr. Skin infections in Egyptian renal transplant recipients.
Transpl Infect Dis 2011: 13: 131–135. All rights reserved Background. The risk of skin infections in renal transplant recipients (RTRs) has been described previously; however, it differs markedly by ethnic groups, skin type, and geographical location. We investigated the prevalence and nature of skin infections in a large series of RTRs in our locality in Egypt. Patients and methods. A total 302 RTRs (216 males and 86 females) were included in this study. They were screened for the presence of bacterial, fungal, and viral skin infections depending on clinical signs, Woods lamp examinations, culture, and biopsy if indicated. The patients were compared with 300 healthy controls matched for age and sex (200 males and 100 females) Results. We found 191 (63.25%) RTRs had some kind of skin infection. Folliculitis (10.3%), tinea versicolor (30.1%), dermatophytosis (19.5%), and onychomycosis (7.6%) were statistically significantly more common in RTRs compared with control subjects. Conclusion. Our RTRs have higher prevalence rates of folliculitis and superficial fungal infections than the healthy population and they should be searched for in every patient with renal transplantation to ensure early treatment and avoid complications. Low‐dose ketoconazole should be considered in renal transplant populations with high rates of superficial fungal infections, as it may reduce risk of such infections.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

Graft-versus-host disease after liver transplantation is associated with bone marrow failure,hemophagocytosis, and DNMT3A mutations

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

     

Tacrolimus for the prevention and treatment of rejection of solid organ transplants

Since its introduction to the antirejection armamentarium in 1994, tacrolimus has become the workhorse of transplant professionals for avoidance of solid organ transplant rejection. Not only does tacrolimus have potent immunosuppressive qualities that prevent rejection, but dosing is straight forward and it is generally well tolerated. However, in the long term, conditions such as calcineurin inhibitor nephrotoxicity can become a problem. A discussion of the compound, the pharmacokinetics, history, and current approved uses for tacrolimus is described. Indeed, tacrolimus is the most important drug for preventing transplant rejection. However, the increased appreciation for significant side effects, particularly in the long term, has led to building interest in new agents with different mechanisms of action and different metabolism.     

Potential and limitations of regulatory T-cell therapy in solid organ transplantation

Over the past few years, the therapeutic potential of Treg has been highlighted in the field of autoimmune diseases and after allogeneic transplantation. The first hurdle for the therapeutic use of Treg is their insufficient numbers in non-manipulated individuals, in particular when facing strong immune activation and expanding effector cells, such as in response to an allograft. Here we review current approaches being explored for Treg expansion in the perspective of clinical therapeutic protocols. We describe different Treg subsets that could be suitable for clinical application, as well as discuss factors such as the required dose of Treg, their antigen-specificity and in vivo stability, that have to be considered for optimal Treg-based immunotherapy in transplantation. Since Treg may not be sufficient as stand-alone therapy for solid organ transplantation in humans, we draw attention to possible hurdles and combination therapy with immunomodulatory drugs that could possibly improve the in vivo efficacy of Treg.     

Unravelling the complexity of cancer–immune system interplay

The immune system has an intricate and complex relationship with tumorigenesis; while it has the capacity to identify and eliminate cancerous cells, the emergence of a tumor signifies its failure to do this. Thus, the immune–tumor interplay is paradoxical as through initial suppression of tumor growth, an immunologically silent or even suppressive tumor evolves. Furthermore, certain immune processes, such as chronic inflammation and immunosuppression, can facilitate malignant progression. Nevertheless, immunotherapeutic approaches can manipulate the immune milieu to improve the therapeutic outcomes of cancer treatments. Furthermore, particular conventional cancer therapies also have immunostimulatory properties in their own right. An in-depth understanding of the intimate involvement of the immune system in tumorigenesis and the potential to manipulate this interaction to improve disease outcomes will enable the development of new and broadly effective cancer therapies.